Abstract 380: Gadolinium Decreases Inflammation Related to Myocardial Ischemia and Reperfusion Injury
The lanthanide cation, gadolinium (Gd) protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. Gd interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that Gd protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of Gd treatment for reperfusion injury on
circulating monoctye and neutrophil counts,
secretion of inflammatory cytokines, and
influx of neutrophils into the myocardium. Rats (n=6/gp) were treated with saline or Gd (20 μmol/kg) 15 min prior to a 30 min period of regional ischemia and 2 hours reperfusion. Sham rats were not subject to ischemia and reperfusion.
Gd did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. Gd decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both control and Gd treated rats. Likewise, IL-8 levels increased throughout the 3 hour time period in the Sham group. There was no difference in IL-8 detected in the myocardium after 2 hours reperfusion between groups. In contrast, after 2 hours reperfusion Gd decreased the myocardial tissue levels of macrophage secreted cytokines, GM-CSF and IL-1. Furthermore, Gd decreased myeloperoxidase (MPO) activity, a marker of neutrophil infiltration in the myocardium after 2 hours of reperfusion. Gd decreased MPO activity to levels below those measured in the Sham group. Gd treatment prior to ischemia and reperfusion injury decreases circulating monocytes and neutrophils, macrophage secreted cytokines, and neutrophil infiltration into injured myocardium. These results suggest Gd decreases monoctye and neutrophil migration and activation and may be a novel treatment for inflammation during ischemia and reperfusion.